Prognostic factors affecting the natural history of node-negative breast cancer

We undertook a natural history investigation of a broad selection of prognostic factors in a cohort of women with node-negative breast cancer. The cohort consisted of 415 consecutive histologic node-negative (T1-3, M0) patients, operated on for primary breast cancer at Women's College Hospital, Toronto, Canada, between 1977 and 1986. Only 7% of these patients were given adjuvant systemic therapy; further, for the 48% of women who underwent lumpectomy, only 29% received adjuvant radiotherapy to the breast. Paraffin-embedded tumour tissue was available for the majority of patients. The following factors were examined for their univariate and multivariate effects on time to recurrence outside the breast (DFI) and survival from breast cancer (DSS): age, weight, tumour size, estrogen receptor, progesterone receptor, histologic type, tumour grade, nuclear grade, lymphovascular invasion, overexpression of neu oncoprotein, DNA ploidy, % cells in S-phase, and adjuvant therapy. Multivariate analyses utilized a Cox model with a step-wise factor selection for the 260 patients with complete information. A worse prognosis was indicated when there was lymphovascular invasion (for DFI, p < 0.001; for DSS, p = 0.0046), high %S-phase (for DFI, p = 0.08; for DSS, p = 0.02), high tumour grade (for DFI, p = 0.02; for DSS, p = 0.03), and overexpression of neu oncoprotein (for DSS, p = 0.07). In our natural history investigation, two factors, lymphovascular invasion and tumour grade, are of particular interest since they may be readily incorporated into clinical practice. Overexpression of neu oncoprotein may also play a role in determining prognosis for women administered adjuvant systemic therapy.